tbuckley/cabot-search huggingface dataset:
P11.03.A DOES REGULAR SURVEILLANCE IMAGING IMPROVE SURVIVAL IN GLIOBLASTOMA? RESULTS FROM A NATIONAL, MULTI-CENTRE COHORT STUDY (INTERVAL-GB)
Authors: C S Gillespie, E R Bligh, M T C Poon, G Solomou, M Gough, A I Islim, C P Millward, O Rominiyi, R Zakaria, S J Price, C Watts, S Camp, T Booth, G Thompson, S J Mills, A Waldman, P Brennan, M D Jenkinson
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Glioblastoma is the most common malignant primary brain tumour in adults and is usually incurable. Post-operative magnetic resonance imaging (MRI) is used to assess extent of resection, and subsequent follow-up MRI is used to monitor response to treatment and to detect progression. The benefit of regular, scheduled follow-up MRI on patient management and outcomes is unclear. MATERIAL AND METHODS In this multi-centre, retrospective observational cohort study we included patients with a histopathologically confirmed glioblastoma, operated between August 31, 2018 and February 1, 2019 who received any adjuvant oncological treatment. Follow-up MRI schedules, indications, and clinical outcomes were collected. The primary objective was to investigate the follow-up MRI surveillance practice after surgery for glioblastoma and assess compliance with recommendations from the National Institute for Health and Care Excellence (NICE) (Post-operative scan &amp;lt;72 hrs, MRI every 3-6 months). The secondary objectives were to determine indications for MRI scans and the association on overall survival (OS) and progression-free survival (PFS). RESULTS 754 patients, with a median age of 63 years (range: 21-84) from 26 neuro-oncology centres were included. Most patients had post-operative MRI within 72 hours of surgery (88.1%, N=407/462). The median number of subsequent follow-up MRI was 1 (Interquartile range 0-4). 28.1% of patients had follow-up MRI in accordance with NICE recommendations (N=212/754). Patients in this group were more likely to receive second-line chemotherapy (28.6% vs 19.5%, P=0.009). The median follow-up period was 10.5 months (IQR 5.3-19.4 months). Median overall survival was 15.1 months (95% CI 12.9-17.3) in the scheduled MRI group and 9.1 months (95% CI 7.8-10.4) in the non-compliant group. On multivariable cox regression analysis, regular, scheduled MRI was independently associated with longer overall survival (HR 1.67, 95% CI 1.33-2.10, P&amp;lt;0.001), but not PFS (HR 1.20, 95% CI 0.98-1.47, P=0.074). Patients with progression first detected on scheduled imaging had a significantly longer OS (18.4 vs 15.6 months, P=0.013) and PFS (9.9 months vs 7.9 months, P=0.041). CONCLUSION Following regular scheduled surveillance follow-up MRI for glioblastoma is associated with longer overall survival. Prospective trials are needed to determine whether regular or symptom-directed MRI influences survival outcomes and quality of life.
P19.04.B EXAMINATION OF THE ROLES OF KDM6A AND KDM6B HISTONE DEMETHYLASES IN ISOCITRATE DEHYDROGENASE (IDH) MUTANT GLIOMA
Authors: S Sarac, E Yilmaz, A Kayabolen, T Bagci Onder
Journal: Neuro-Oncology (2023)

Abstract Glioma, comprising 80% percent of all malignant brain tumors, is one of the most aggressive and difficult to treat tumors. Isocitrate dehydrogenase (IDH) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing α-ketoglutarate. Most IDH-mutant gliomas have a heterozygous point mutation in IDH1 that causes an arginine-to-histidine substitution at amino acid 132. Mutant IDH enzyme leads to 2-hydroxyglutarate accumulation in cells, inhibiting DNA and histone demethylases and ultimately generating a hypermethylated epigenetic phenotype. Considering that the mutant IDH enzyme generates a discrete epigenetic profile, we aimed to develop an epigenetic-based therapy approach for IDH mutant glioma. To this end, we performed chemical library screens consisting of inhibitors of important epigenetic enzymes and identified GSK-J4 as a chemical selectively targeting IDH1 mutant cells.GSK-J4 is a well-known inhibitor for histone demethylases KDM6A and KDM6B; therefore, we aimed to phenocopy the effects of the chemical approach with the genetic approach by depleting KDM6A and/or KDM6B using CRISPR/Cas9. We successfully established IDH-mutant primary glioma cell lines deficient in KDM6A and/or KDM6B expression, as revealed by qRT-PCR and Western Blots. Cells with double knockout were markedly slower in growth compared to controls which had received nontargeting gRNA or single gRNAs targeting each enzyme. In the future, we will examine changes in cell cycle and apoptosis pathways upon KDM6A and KDM6B knockouts and test the response of these cells to mutant IDH inhibitors, TMZ, or irradiation. In parallel, genome-wide changes in gene expression and cellular pathways, histone modifications, and chromatin accessibility will be analyzed, via RNA-seq, ChIP-seq, and ATAC-seq techniques, respectively.Even though KDM6A and KDM6B have been shown to have important but sometimes conflicting roles in various tumor types, no study showed their roles in IDH mutant glioma. Therefore, revealing the functional mechanisms of KDM6A and KDM6B in IDH-mutant gliomas will serve as an important step that leads to the development of novel epigenetic-based therapeutic approaches for IDH-mutant gliomas.This project is supported by TUBITAK with the given grant number: 219S882.
P17.03.A MAGIC-G1: A PHASE 1 DOSE-ESCALATION TRIAL OF WEEKLY INTRATUMORAL ADMINISTRATION OF THE SOLUBILISED FORMULATION OF PANOBINOSTAT (MTX110) IN PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM)
Authors: A Desjardins, H Barnes, R Davies, G Grant, R Cavaliere, E Sauvageau, D Zamoryakhin
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND One of the biggest challenges in treating rGBM is achieving high local drug concentration. Convection enhanced delivery (CED) is a ‘direct-to-brain’ drug delivery method that previously demonstrated its usefulness in overcoming the blood-brain barrier, while also limiting systemic toxicity. MTX110 (Midatech Ltd), a water-soluble formulation of panobinostat, has demonstrated cytotoxic activity in GBM cell lines, as well as safety and efficacy in two pediatric diffuse pontine glioma trials. Delivery of MTX110 via an implanted pump and CED catheter system in patients with GBM appears to be an attractive treatment option, that allows for therapeutic doses of the drug to be delivered weekly directly to the tumor, thus avoiding systemic administration and therefore toxicity. MATERIAL AND METHODS Eligibility includes adult rGBM patients with a single enhancing lesion ≤3cm in maximal diameter; ≥4 weeks after chemotherapy, bevacizumab, or study drug; adequate organ function; and KPS ≥60%. MTX110 is continuously infused over 48hrs weekly at a rate of 0.5mL/h, via a CED catheter implanted into the enhancing disease recurrence connected to a fully internalized pump system. After safety of a single patient treated at 60μM has been established, 3-6 patients will be treated with MTX110 at 90μM as a single agent (Cohort 1). Patients in cohort 2 will receive MTX110 in combination with lomustine at a starting MTX110 dose of 60 μM and following the same dose-escalation approach. RESULTS As of March 30, 2023, the 1st patient was treated in monotherapy at 60μM and has received 12 weekly infusions of MTX110. No dose-limiting toxicities were observed. Observed study related adverse events (AEs) included: grade 1 cognitive disturbance, headache, and seizure; grade 2 candida wound infection, erythema of the scalp, bruising, and hemiparesis; and grade 3 abdominal seroma at pump insertion site. Enrolment is ongoing and the next patient will receive the 90 μM dose. CONCLUSION Weekly intratumoral administration of MTX110 via a fully internally implanted CED pump system is feasible. Updated results will be presented.
P11.16.B THE MAYO CLINIC MULTIDISCIPLINARY NF2 CLINIC EXPERIENCE OF BEVACIZUMAB IN NEUROFIBROMATOSIS TYPE 2-RELATED SCHWANNOMATOSIS PATIENTS WITH VESTIBULAR SCHWANNOMAS
Authors: M J Webb, L M Webb, J J Van Gompel, M J Link, B A Neff, M L Carlson, C W Driscoll, M W Ruff, K A Anderson, B J Neth, S H Kizilbash, J H Uhm, J I Lane, J C Benson, D J Blezek, P M Mehta, G Bathla, U T Sener
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Neurofibromatosis type 2-related schwannomatosis (NF2) is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS) as well as other nervous system tumors. Management decisions for NF2-related VS are typically predicated on tumor size, associated symptoms, patient age, and comorbidities. Observation, surgical resection, and stereotactic radiosurgery can be viable options. In patients with VS associated with NF2, vascular endothelial growth factor A (VEGF-A) inhibitor, bevacizumab, is a systemic treatment option. In this single institution study, we review our clinical experience in patients with NF2 who received bevacizumab for VS and evaluate the effect of bevacizumab treatment on VS growth and symptom progression. MATERIAL AND METHODS This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Three-dimensional volumetric data for VS were measured using manual segmentation with Visage PACS software under the direct supervision of a board-certified neuroradiologist. RESULTS Out of 76 patients with NF2 evaluated in the past 3 years, we identified 19 that received treatment with bevacizumab. Median age of NF2 diagnosis was 19 years (range 0.5-61) with a median NF2 phenotype severity score of 2 (range 1-3). Thirteen of these patients have discontinued bevacizumab, accounting for a median duration of 12.2 months (range 3.3-88 months) of bevacizumab treatment. Bevacizumab was discontinued due to hypertension (n=5), proteinuria and renal dysfunction (n=3), tumor progression (n=2), fatigue or other intolerance (n=2), or non-compliance (n=1). The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March 2023 (range 3.7-48.3 months). Fifteen patients had brain MRI data available to evaluate VS change during bevacizumab treatment, with partial response observed in 5 patients, stable disease in 8, and progression in 2. Ten of the 13 patients who stopped bevacizumab had MRI data to evaluate VS change following treatment termination. Within 6 months of bevacizumab discontinuation, 6 patients had rebound growth of their VS between 21-95% from their previous tumor volume, while 4 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. CONCLUSION Our single institution experience confirms that bevacizumab can slow progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.
P01.03.B COGNITIVE REHABILITATION IN PRIMARY BRAIN CANCER: BASELINE PATIENT CHARACTERISTICS AND NEUROPSYCHOLOGICAL ASSESSMENTS
Authors: E Smith, C Weyer-Jamora, T L Luks, P M Bracci, M Brie, S L Hervey-Jumper, R Almomen, S Phan, J G Rottgering, S M Chang, J W Taylor
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Cognitive impairments are a common issue for individuals with primary brain tumors. Cognitive rehabilitation is a known effective treatment in other neurologic diseases, with emerging data in adults with brain tumors. However, there is a limited understanding of the clinical characteristics of the patients referred to cognitive rehabilitation in this population. MATERIAL AND METHODS We identified a cohort of adult primary brain tumor patients who were clinically referred for consideration of cognitive rehabilitation by their treating neuro-oncologist at the University of California San Francisco (UCSF) between 05/2018 - 07/2022. Baseline neurocognitive impairments were assessed both at the individual test and domain levels. We analyzed absolute impairments and incorporated relative impairments for a subset of patients using a word reading task (WTAR) for pre-morbid estimates. Absolute impairments were defined as a Z-score of -1.5 or below. Relative impairments were defined as a Z-score at least 1.5 standard deviations below the pre-morbid estimate. A two-sample test was used to assess differences between relative and absolute impairments. RESULTS We evaluated 136 patients with primary brain tumors. The median age was 53 years (range 21-78), with majority male (62.5%), white (61.8%), and at least 16 years of education (79.4%). Astrocytomas (36.0%) and oligodendrogliomas (27.2%) were the most common diagnoses with most tumors located in the frontal lobe (54.4%) and in the left hemisphere (52.2%). The mean time from pathologic diagnosis to testing was 3.12 years (range: -0.83 to 24.18) with 73.5% having prior radiation. Neuropsychological evaluation identified several impaired domains, with significantly more relative impairments based on premorbid estimates versus absolute (p=.01). The most commonly impaired domains for both relative and absolute impairments were processing speed at 90.6% and 43.4%; verbal learning and memory at 67.6% and 38.2%; and executive/frontal systems at 53.3% and 25%. Relative and absolute impairments for auditory attention/concentration at 46.8% and 14.1%; language abilities at 44.1% and 15.2%; and visuospatial learning and memory at 33. 3% and 21.2% were somewhat less common. CONCLUSION These results provide a landscape for baseline patient characteristics and cognitive function in a large cohort of primary brain tumor patients who were clinically referred for cognitive rehabilitation. Processing speed and verbal learning and memory were the most relatively affected cognitive domains in this population. We also highlight the importance of incorporating premorbid estimates in determining levels of impairment. Updated data assessing correlations among patient, tumor, treatment characteristics, and cognitive function will be presented.
P15.10.A USE OF DUAL TRACERS PET AS A PREDICTIVE BIOMARKER OF THE SITE OF RECURRENCE IN HIGH GRADE GLIOMA
Authors: B Alfaifi, E Agushi, R Hinz, A Jackson, D Lewis, D Coope
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND High grade glioma has poor survival rate and tumour recurrence occurs despite current treatments. Positron emission tomography (PET) with [11C](R)PK11195 can evaluate translocator protein (TSPO) and [11C]methionine can assess amino acid transport. PET imaging might have the potential to detect tumour regions at baseline that will later develop as the site of recurrence. We compare TSPO measured using [11C](R)PK11195 and amino acid transport using [11C]methionine at baseline and investigate to what extend the two tracers can predict the site of tumour recurrence. MATERIAL AND METHODS Twelve patients with newly diagnosed high grade glioma underwent multimodal imaging studies. Preoperative MRI, [11C](R)PK11195 PET, [11C]methionine PET and postoperative (follow-up) MRI were co-registered. [11C](R)PK11195 binding potential (BPND) maps were generated using the simplified reference tissue model with grey matter cerebellar time-activity curve as tissue input function. [11C]methionine uptake was calculated as tumour to background ratio (TBR). Contrast enhancing volumes of interest (VOI) were defined on T1W post contrast. The VOI of [11C]methionine high uptake was standardized as TBR&amp;gt;1.7. For [11C](R)PK11195 VOI, the mean BPND + SD of grey matter voxels was calculated from individual maps of healthy control (HC; n = 50). Afterward, 95% confidence interval threshold (HC mean + 1.96 × SD) was used to describe high voxel activity in tumour (BPND&amp;gt;0.35). Tumour recurrence VOI was defined as contrast enhancement on the follow-up images. RESULTS The mean percentage overlap between high [11C](R)PK11195 BPND and [11C]methionine uptake was 48±17%. The mean percentage of each VOI showing exclusively high [11C](R)PK11195 BPND or exclusively high [11C]methionine was 25±21 or 27±22 respectively. The mean percentage overlap between high [11C](R)PK11195 and contrast enhancement is 36±14. The mean percentage of exclusively hight [11C](R)PK11195 or exclusively contrast enhancement were 38±18 or 26±25 respectively. The mean percentage overlap between high [11C]methionine and contrast enhancement were 47±12. The mean percentage of exclusively [11C]methionine or contrast enhancement were 36±20 or 17±17 respectively. The percentage volume overlap between contrast enhancing regions at recurrence and baseline [11C](R)PK11195 or [11C]methionine was 20±13 or 25±13 respectively. CONCLUSION The two PET tracers have high overlap although some regions are specific for high TSPO binding without high methionine uptake which could reflect an inflammatory component within the tumour microenvironment. The common regions between methionine and contrast enhancement is larger than TSPO binding which could represent that TSPO binding is less effected by disrupted blood-brain barrier. The mean percentage overlap with VOI representing tumour recurrence were similar.
P08.03.A CAREGIVERS OF ADULT NEURO-ONCOLOGICAL PATIENTS: UNMET NEEDS AND RELEVANT PROBLEMS - A PROSPECTIVE STUDY
Authors: M Spieker, M Rapp, D Rieger, P Bombach, S Kurz, M Tatagiba, M Sabel, G Tabatabai, M Renovanz
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND The diagnosis of a brain tumor represents high burden for patients’ caregivers. Psychosocial screening tools for caregivers adapted to neuro-oncological tumor entities are urgently required but do not exist. To bridge this gap, we aim to develop a problem list in terms of a holistic need assessment tailored to their unmet needs of caregivers for an application in combination to the NCCN distress thermometer scale. MATERIAL AND METHODS First, items of high relevance for the caregivers were identified on basis of retrospective analyses. Second, we prospectively conducted an assessment in two centers: in the first center, caregivers filled out a questionnaire (center A), in the second center, the questionnaire was applied as qualitative interview with caregivers (center B). We performed a qualitative content analysis applying inductive/deductive categorizations of the reports. RESULTS The qualitative interviews included n=11 main questions and up to 4 subquestions focusing on changes in everyday life, relationship, social live, emotional, physical, financial, spiritual problems and support needs. A total of 47 caregivers were assessed (n=25 in center A via questionnaire, n=22 in center B via interviews) during outpatient visits. Most of the caregivers wished for psychological support (27/47, 57%), first contact with psycho-oncologists after first diagnosis (25/47, 53%) or in case of a clinical deterioration (28/47, 59%). Strategies for problem solving (26/47, 55%) and finding sources of strength (22/47, 47%) were most important regarding needed support. Changes in everyday life’ were reported by 87% of caregivers (41/47), including constraints/organization of (medical) appointments (24/47, 51%) or constant availability required for the partner (20/47, 43%). Also, 70% (33/47) put their own interests last or adapt their leisure activities. In the qualitative interviews (Center B), additional items indicating caregiver burden were identified: “dealing with psychological problems of the patient” (3/22, 16%), “different coping strategies among patient and caregiver” (4/22, 18%). Emotional problems, particularly depressive symptoms were addressed more profoundly in the qualitative interviews (“loss of interest and feelings of sadness”, 4/22, 18%). CONCLUSION The interviews reflected the unmet needs of brain tumor caregivers and allow for the targeted assessment of the specific burdens. Furthermore, we were able to gather more in-depth information per qualitative interviews.
P21.07.B THE LHSC/WESTERN BRAIN TUMOUR TISSUE BANK: A GLOBAL RESOURCE
Authors: J Megyesi, R Wang, M White, A Ranger, D Ramsay, Q Zhang
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND A brain tumour tissue bank can serve as an important source of tissue for neuro-oncology research. The London Health Sciences (LHSC) / Western Brain Tumour Tissue Bank (BTTB) provides high-quality brain tumour tissue specimens that are used globally for neuro-oncology research. The LHSC / Western BTTB was established approximately 35 years ago. The objectives of this study were to: 1) establish an up-to-date accounting of the brain tumour specimens in the BTTB; 2) compare the quality control measures used to assess specimen quality against those used in other comparable tissue banks; 3) determine the scope of tissue distribution globally. MATERIAL AND METHODS The records of the BTTB were reviewed with the assistance of the BTTB coordinator. Number and type of brain tumour specimens were recorded. The quality control measures used in the BTTB were compared with the published literature. The location of laboratories to which brain tumour tissue had been distributed was determined. RESULTS Since 1995 there have been 1536 adult brain tumour specimens collected in the BTTB. There are approximately 3 vials per case, not including paraffin blocks. This includes 713 primary intra-axial central nervous system tumours, 229 meningeal tumours, and 285 metastatic tumours. Since 1995 there have been 223 pediatric brain tumour specimens collected in the BTTB. This includes 53 pilocytic astrocytomas, 32 medulloblastomas, and 27 ependymomas. The quality control measures used in the BTTB appear to exceed those used by other brain tumour tissue banks as determined by literature review. The BTTB has sent tissue specimens to neuro-oncology laboratories around the globe and numerous publications have resulted from experiments using the brain tumour tissue supplied by the BTTB. CONCLUSION The LHSC / Western BTTB has collected a large and diverse number of high quality brain tumour specimens since its founding. It serves as a global resource, and the supplied tissue has led to many research publications in neuro-oncology.